Granulocytes-colony stimulating factor (G-CSF) based stem cell therapy in myocardial infarction

Hyun-Jae Kang, Hyo-Soo Kim

Department of Internal Medicine, College of Medicine, Seoul National University

Bone marrow stem cell transplantation in myocardial infarction showed favorable outcome in animal study and recent clinical trials. G-CSF based stem cell therapy also has been regarded as a promising strategy. G-CSF has been used as an efficient and safe stem cell mobilizer in clinical practice. G-CSF based stem cell therapy has advantages of noninvasiveness and easiness of procedure compared to bone marrow stem cell transplantation. Additionally G-CSF itself can improve cardiac function and cardiac remodeling in myocardial infarction via mechanisms other than stem cell mobilization. However G-CSF based stem cell therapy bought concerns about aggravation of inflammation and re-stenosis of coronary artery.

We compared two methods of G-CSF based stem cell therapy - G-CSF induced mobilization alone and intra-coronary infusion of collected stem cells which were mobilized by G-CSF - in Myocardial Regeneration and Angiogenesis in Myocardial Infarction with G-CSF and Intra-Coronary Stem Cell Infusion (MAGIC Cell) clinical trial. In MAGIC Cell trial, we had a presumptive conclusion that intra-coronary infusion of mobilized stem cells improved cardiac function and remodeling but G-CSF mobilization alone did not. The improvement in cardiac function with intra-coronary infusion of mobilized stem cells by G-CSF was comparable to that of bone marrow stem cell transplantation. Additionally G-CSF based stem cell therapy showed statistically insignificant aggravation of re-stenosis. Aggravation of neointimal growth with G-CSF might be explained by two aspects: timing of G-CSF administration and G-CSF itself. However, In vitro and in vivo experiment paclitaxel eluting stent can prevent promotion of re-stenosis which was induced by G-CSF. And, we evaluated the effect of drug eluting stent in clinical trial. We also evaluated concerns about aggravation of inflammation and vascular instability related to G-CSF. In our study, G-CSF based stem cell therapy did not aggravate endothelial function and effectively mobilize stem cells in patients with myocardial infarction. Possible risk of aggravation of re-stenosis can be overcome by adoption of drug eluting stent and modification of administration of G-CSF. G-CSF based stem cell therapy can be used as one of the promising strategy of stem cell therapy in patients with myocardial infarction.